BibTex format
@article{Mathavan:2022:10.1021/acsmedchemlett.2c00248,
author = {Mathavan, I and Liu, LJ and Robinson, SW and El-Sakkary, N and Elastico, AJJ and Gomez, D and Nellas, R and Owens, RJ and Zuercher, W and Navratilova, I and Caffrey, CR and Beis, K},
doi = {10.1021/acsmedchemlett.2c00248},
journal = {ACS Medicinal Chemistry Letters},
pages = {1715--1722},
title = {Identification of inhibitors of the Schistosoma mansoni VKR2 kinase domain},
url = {http://dx.doi.org/10.1021/acsmedchemlett.2c00248},
volume = {13},
year = {2022}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Schistosomiasis is a neglected tropical disease caused by parasitic flatworms. Current treatment relies on just one partially effective drug, praziquantel (PZQ). Schistosoma mansoni Venus Kinase Receptors 1 and 2 (SmVKR1 and SmVKR2) are important for parasite growth and egg production, and are potential targets for combating schistosomiasis. VKRs consist of an extracellular Venus Flytrap Module (VFTM) linked via a transmembrane helix to a kinase domain. Here, we initiated a drug discovery effort to inhibit the activity of the SmVKR2 kinase domain (SmVKR2KD) by screening the GSK published kinase inhibitor set 2 (PKIS2). We identified several inhibitors, of which four were able to inhibit its enzymatic activity and induced phenotypic changes in ex vivoS. mansoni. Our crystal structure of the SmVKR2KD displays an active-like state that sheds light on the activation process of VKRs. Our data provide a basis for the further exploration of SmVKR2 as a possible drug target.
AU - Mathavan,I
AU - Liu,LJ
AU - Robinson,SW
AU - El-Sakkary,N
AU - Elastico,AJJ
AU - Gomez,D
AU - Nellas,R
AU - Owens,RJ
AU - Zuercher,W
AU - Navratilova,I
AU - Caffrey,CR
AU - Beis,K
DO - 10.1021/acsmedchemlett.2c00248
EP - 1722
PY - 2022///
SN - 1948-5875
SP - 1715
TI - Identification of inhibitors of the Schistosoma mansoni VKR2 kinase domain
T2 - ACS Medicinal Chemistry Letters
UR - http://dx.doi.org/10.1021/acsmedchemlett.2c00248
UR - http://hdl.handle.net/10044/1/100347
VL - 13
ER -